Drugs efficacy evaluation - corrector VX-809 and potentiator VX-770 - on CFTR (cystic fibrosis transmembrane conductance regulator) protein function in primary respiratory and intestinal epithelial cells from patients with cystic fibrosis

• Grant number: 14/14666-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Antonio Fernando Ribeiro
• Grantee: Antonio Fernando Ribeiro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Adyléia Aparecida Dalbo Contrera Toro ; Carmen Sílvia Bertuzzo ; Jose Dirceu Ribeiro ; Margarida Sofia Pereira Duarte Amaral

Abstract

Cystic fibrosis (CF) is a lethal autosomal recessive disease with clinical manifestationsthat compromise the digestive, reproductive and mainly the respiratory system. It is caused bymutations in the CFTR gene encoding Cl- channel in the apical membrane of epithelial cells. It was described about 2000 mutations in CFTR and the F508del is the most frequent mutation (about 90% of patients). In Brazil, however, this mutation is less frequent (about 65%), occurring rare mutations and atypical forms of the disease. The discovery of compounds capable to correct the CFTR defect indicates that the repair of this channel specific mutations it is possible and can be realized with respect to DNA, RNA, and especially the protein. The VX-809 and VX-770 drugs are already in clinical trials in developed countries, with significant benefits to patients. Our research group is pioneer in the use of techniques that aid the differential diagnosis of CF (sweat rate evaluation detected by Evaporimeter after ²-adrenergic stimulation and Cl- secretion mediated by CFTR channel in rectal biopsies, usingelectrophysiology). In this project, we propose to evaluate the VX-809 and VX-770 preclinicalefficacy in Brazilian population through new methodologies, based on the cultivation andanalysis of primary respiratory cells, intestinal biopsy, and CFTR transcripts characterization.The knowledge of these drugs effectiveness can target their use in personalized medicine. (AU)